Nitric oxide : biology and chemistry最新文献

{"title":"Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity","authors":"D.V. Chartoumpekis ,&nbsp;I. Chen ,&nbsp;S.R. Salvatore ,&nbsp;F.J. Schopfer ,&nbsp;B.A. Freeman ,&nbsp;N.K.H. Khoo","doi":"10.1016/j.niox.2024.06.002","DOIUrl":"10.1016/j.niox.2024.06.002","url":null,"abstract":"<div><p>Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO₂-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO₂-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO₂-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO₂-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2^fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO₂-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO₂-OA for 48 days), both HFD-fed Nrf2^fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO₂-OA treatment, no distinction was observed between Nrf2^fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2^fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2^fl/fl and ANKO compared to LFD-fed Nrf2^fl/fl mice. Notably, NO₂-OA treatment improved glucose tolerance in HFD-fed Nrf2^fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO₂-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000776/pdfft?md5=ad2f79fdb7ebaa2e2587ac6ddb7537ad&pid=1-s2.0-S1089860324000776-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An observational analysis on the influence of parental allergic rhinitis, asthma and smoking on exhaled nitric oxide in offspring","authors":"S. Zaigham ,&nbsp;R.J. Bertelsen ,&nbsp;S.C. Dharmage ,&nbsp;V. Schlünssen ,&nbsp;N.O. Jögi ,&nbsp;L. Palacios Gomez ,&nbsp;M. Holm ,&nbsp;A. Oudin ,&nbsp;M.J. Abramson ,&nbsp;T. Sigsgaard ,&nbsp;R. Jõgi ,&nbsp;C. Svanes ,&nbsp;A.C. Olin ,&nbsp;B. Forsberg ,&nbsp;C. Janson ,&nbsp;E. Nerpin ,&nbsp;A. Johannessen ,&nbsp;A. Malinovschi","doi":"10.1016/j.niox.2024.06.001","DOIUrl":"10.1016/j.niox.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><p>Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring.</p></div><div><h3>Methods</h3><p>We studied 609 offspring aged 16–47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors.</p></div><div><h3>Results</h3><p>Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0–37.7], p = 0.008, and 13.8 % [0.4–28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9–33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors.</p></div><div><h3>Conclusions</h3><p>Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000764/pdfft?md5=82733d116ee630e9b41a516c46b1baac&pid=1-s2.0-S1089860324000764-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum protein of 57 kDa sulfhydration promotes intestinal calcium absorption to attenuate primary osteoporosis","authors":"Huifang Liu ,&nbsp;Yang Zheng ,&nbsp;Fuming Li ,&nbsp;Bin Geng ,&nbsp;Feng Liao","doi":"10.1016/j.niox.2024.05.004","DOIUrl":"10.1016/j.niox.2024.05.004","url":null,"abstract":"<div><p>Endogenous hydrogen sulfide (H₂S) plays an important role in bone metabolism. However, the exact role of H₂S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H₂S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H₂S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca²⁺ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H₂S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H₂S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca²⁺, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H₂O₂) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H₂O₂ stimulation and restored by DL-dithiothreitol. These findings suggest that H₂S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000752/pdfft?md5=459653b0d397adc1664e7eb514afff00&pid=1-s2.0-S1089860324000752-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging the redundancy of S-denitrosylases in response to S-nitrosylation of caspases: Experimental strategies and beyond","authors":"Surupa Chakraborty,&nbsp;Akansha Mishra ,&nbsp;Ankita Choudhuri ,&nbsp;Tamal Bhaumik,&nbsp;Rajib Sengupta","doi":"10.1016/j.niox.2024.05.002","DOIUrl":"10.1016/j.niox.2024.05.002","url":null,"abstract":"<div><p>Redox-based protein posttranslational modifications, such as S-nitrosylation of critical, active site cysteine thiols have garnered significant clinical attention and research interest, reasoning for one of the crucial biological implications of reactive messenger molecule, nitric oxide in the cellular repertoire. The stringency of the S-(de)nitrosylation-based redox switch governs the activity and contribution of several susceptible enzymes in signal transduction processes and diverse pathophysiological settings, thus establishing it as a transient yet reasonable, and regulated mechanism of NO adduction and release. Notably, endogenous proteases like cytosolic and mitochondrial caspases with a molecular weight ranging from 33 to 55 kDa are susceptible to performing this biochemistry in the presence of major oxidoreductases, which further unveils the enormous redox-mediated regulational control of caspases in the etiology of diseases. In addition to advancing the progress of the current state of understanding of ‘redox biochemistry’ in the field of medicine and enriching the existing dynamic S-nitrosoproteome, this review stands as a testament to an unprecedented shift in the underpinnings for redundancy and redox relay between the major redoxin/antioxidant systems, fine-tuning of which can command the apoptotic control of caspases at the face of nitro-oxidative stress. These intricate functional overlaps and cellular backups, supported rationally by kinetically favorable reaction mechanisms suggest the physiological relevance of identifying and involving such cognate substrates for cellular S-denitrosylases that can shed light on the bigger picture of extensively proposing targeted therapies and redox-based drug designing to potentially alleviate the side effects of NOx/ROS in disease pathogenesis.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial dysfunction in Sickle Cell Disease: Strategies for the treatment","authors":"Aline Renata Pavan ,&nbsp;Barbara Terroni ,&nbsp;Jean Leandro Dos Santos","doi":"10.1016/j.niox.2024.05.003","DOIUrl":"10.1016/j.niox.2024.05.003","url":null,"abstract":"<div><p>Sickle Cell Anemia (SCA), is an inherited hemoglobinopathy characterized by the presence of an abnormal hemoglobin (HbS), being the most prevalent sickle cell disease (SCD). SCA is characterized by vascular endothelial dysfunction, which contributes significantly to various clinical conditions, including but not limited to pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke. The pathophysiology of endothelial dysfunction (ED) in SCA is a multifaceted process involving a chronic inflammatory and hypercoagulable state. Key factors include hemolysis-associated elements like reduced arginine and nitric oxide (NO) availability, elevated levels of vascular adhesion molecules, the uncoupling effect of NO synthase, heightened arginase activity, an environment characterized by oxidative stress with the production of reactive oxygen and nitrogen species, and occurrences of ischemia-reperfusion injury, along with apolipoprotein A-1 depletion. The urgency for novel interventions addressing ED is evident. Presently, there is a focus on investigating small molecules that disrupt the arginine-nitric oxide pathway, exhibiting anti-inflammatory and antioxidant properties while diminishing levels of cellular and vascular adhesion molecules. In this mini-review article, we delve into the progress made in strategies for treating ED in SCD with the aim of cultivating insights for drug design.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide protects intestinal mucosal barrier function and prevents acute graft rejection after intestinal transplantation: A mini-review","authors":"George J. Dugbartey ,&nbsp;Deborah Nanteer ,&nbsp;Ivy Osae","doi":"10.1016/j.niox.2024.05.001","DOIUrl":"10.1016/j.niox.2024.05.001","url":null,"abstract":"<div><p>Intestinal transplantation is a complex technical procedure that provides patients suffering from end-stage intestinal failure an opportunity to enjoy improved quality of life, nutrition and survival. Compared to other types of organ transplants, it is a relatively new advancement in the field of organ transplantation. Nevertheless, great advances have been made over the past few decades to the present era, including the use of ischemic preconditioning, gene therapy, and addition of pharmacological supplements to preservation solutions. However, despite these strides, intestinal transplantation is still a challenging endeavor due to several factors. Notable among them is ischemia-reperfusion injury (IRI), which results in loss of cellular integrity and mucosal barrier function. In addition, IRI causes graft failure, delayed graft function, and decreased graft and recipient survival. This has necessitated the search for novel therapeutic avenues and improved transplantation protocols to prevent or attenuate intestinal IRI. Among the many candidate agents that are being investigated to combat IRI and its associated complications, nitric oxide (NO). NO is an endogenously produced gaseous signaling molecule with several therapeutic properties. The purpose of this mini-review is to discuss IRI and its related complications in intestinal transplantation, and NO as an emerging pharmacological tool against this challenging pathological condition. i</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships between nitric oxide biomarkers and physiological outcomes following dietary nitrate supplementation","authors":"Chenguang Wei,&nbsp;Anni Vanhatalo,&nbsp;Matthew I. Black,&nbsp;Jamie R. Blackwell,&nbsp;Raghini Rajaram,&nbsp;Stefan Kadach,&nbsp;Andrew M. Jones","doi":"10.1016/j.niox.2024.04.010","DOIUrl":"10.1016/j.niox.2024.04.010","url":null,"abstract":"<div><p>Dietary nitrate (NO₃⁻) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO₂⁻]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO₃⁻, NO₂⁻, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO₃⁻ supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO₃⁻-rich beetroot juice (BR) (∼12.8 mmol NO₃⁻) and NO₃⁻-depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5–3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (−2 ± 3 mmHg, <em>P</em> = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0–30 ms (39 ± 57 N m s⁻¹, <em>P</em> = 0.03) and 0–50 ms (79 ± 99 N m s⁻¹, <em>P</em> = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO₂⁻] was correlated with lower diastolic BP (<em>r</em> = −0.68, <em>P</em> = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO₃⁻] was correlated with greater RTD at 0–30 ms (<em>r</em> = 0.64<em>, P=</em>0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO₃⁻] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO₃⁻ ingestion in humans.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S108986032400065X/pdfft?md5=aef4e36cffba5496c4beadf4d7c9713d&pid=1-s2.0-S108986032400065X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-mediated delivery of tetrahydrobiopterin restores endothelial function in diabetic rats","authors":"Katherine A. Kelly ,&nbsp;Cristine L. Heaps ,&nbsp;Guoyao Wu ,&nbsp;Vinod Labhasetwar ,&nbsp;Cynthia J. Meininger","doi":"10.1016/j.niox.2024.04.009","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.009","url":null,"abstract":"<div><p>Endothelial dysfunction, underlying the vascular complications of diabetes and other cardiovascular disorders, may result from uncoupling of endothelial nitric oxide synthase (eNOS) activity due to decreased levels of tetrahydrobiopterin (BH4), a critical co-factor for eNOS. Some clinical trials attempting to deliver exogenous BH4 as a potential therapeutic strategy in vascular disease states have failed due to oxidation of BH4 in the circulation. We sought to develop a means of protecting BH4 from oxidation while delivering it to dysfunctional endothelial cells. Polymeric and solid lipid nanoparticles (NPs) loaded with BH4 were delivered by injection or oral gavage, respectively, to streptozotocin-induced diabetic rats. BH4 was measured in coronary endothelial cells and endothelium-dependent vascular reactivity was assessed in vascular rings. Lymphatic uptake of orally delivered lipid NPs was verified by sampling mesenteric lymph. BH4-loaded polymeric NPs maintained nitric oxide production by cultured endothelial cells under conditions of oxidative stress. BH4-loaded NPs, delivered via injection or ingestion, increased coronary endothelial BH4 concentration and improved endothelium-dependent vasorelaxation in diabetic rats. Pharmacodynamics assessment indicated peak concentration of solid lipid NPs in the systemic bloodstream 6 hours after ingestion, with disappearance noted by 48 hours. These studies support the feasibility of utilizing NPs to deliver BH4 to dysfunctional endothelial cells to increase nitric oxide bioavailability. BH4-loaded NPs could provide an innovative tool to restore redox balance in blood vessels and modulate eNOS-mediated vascular function to reverse or retard vascular disease in diabetes.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000521/pdfft?md5=1538ec9258168d27a80e05ecb4b33592&pid=1-s2.0-S1089860324000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages, IL-10, and nitric oxide increase, induced by hyperglycemic conditions, impact the development of murine melanoma B16F10-Nex2","authors":"Tarciso A. Sellani ,&nbsp;Samanta L. Tomaz ,&nbsp;Jéssica M. Gonçalves ,&nbsp;Adriana Lima ,&nbsp;Carolina C. de Amat Herbozo ,&nbsp;Gabrielli N. Silva ,&nbsp;Mônica Gambero ,&nbsp;Ieda M. Longo-Maugéri ,&nbsp;Karin A. Simon ,&nbsp;Hugo P. Monteiro ,&nbsp;Elaine G. Rodrigues","doi":"10.1016/j.niox.2024.04.007","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.007","url":null,"abstract":"<div><p>Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. <em>In vivo</em> neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures <em>in vitro</em>, and B16F10-Nex2 cells incubated with different glucose concentrations <em>in vitro</em> produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH-sensitive release of nitric oxide gas using peptide-graphene co-assembled hybrid nanosheets","authors":"Tanveer A. Tabish ,&nbsp;Jiamin Xu ,&nbsp;Christopher K. Campbell ,&nbsp;Manzar Abbas ,&nbsp;William K. Myers ,&nbsp;Pravin Didwal ,&nbsp;Dario Carugo ,&nbsp;Fang Xie ,&nbsp;Mark J. Crabtree ,&nbsp;Eleanor Stride ,&nbsp;Craig A. Lygate","doi":"10.1016/j.niox.2024.04.008","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.008","url":null,"abstract":"<div><p>Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 μM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S108986032400051X/pdfft?md5=3dd8deb85683d1ce4afd8e1ac3e471e9&pid=1-s2.0-S108986032400051X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}